US2025288683A1PendingUtilityA1
Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
Est. expiryMay 6, 2042(~15.8 yrs left)· nominal 20-yr term from priority
A61K 31/5377A61K 31/529A61K 31/519A61K 31/506A61P 35/00A61K 47/545A61K 47/55C07D 513/22
64
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Claims
Abstract
This disclosure provides compounds of Formula (I) or pharmaceutically acceptable salts thereof, that induce degradation of a BCL-X L protein. These are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also compositions containing the compounds provided herein as well as methods of using and making the same.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
Ring A is phenylene optionally substituted with 1-3R a ;
R 1 is selected from the group consisting of:
(a) C(O)OH,
(b) C(O)NR d R c , and
(c) C(O)OC 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1-3 R c ;
each R 2 , R 3 , R 4 , and R 5 is independently selected from the group consisting of: halo, CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, OH, and NR d R e ;
m2 is 0, 1, or 2;
m3 and m4 are independently 0, 1, 2, or 3;
m5 is 0, 1, 2, 3, or 4;
L is -(L A ) n1 -, wherein L A and n1 are defined according to (AA) or (BB):
(AA)
n1 is an integer from 3 to 12; and
each L A is independently selected from the group consisting of: L A1 , L A3 , and L A4 , provided that 1-3 occurrences of L A is L A4 ;
(BB)
n1 is an integer from 0 to 20; and
each L A is independently selected from the group consisting of: L A1 and L A3 ;
each L A1 is independently selected from the group consisting of: —CH 2 —, —CHR L —, and —C(R L ) 2 —;
each L A3 is independently selected from the group consisting of: —N(R d )—, —N(R b )—, —O—, —S(O) 0-2 —, and C(═O);
each L A4 is independently selected from the group consisting of:
(a) C 3-15 cycloalkylene or 3-15 membered heterocyclylene, each of which is optionally substituted with 1-6 substituents independently selected from the group consisting of: R a and R b ; and
(b) C 6-15 arylene or 5-15 membered heteroarylene, each of which is optionally substituted with 1-6 substituents independently selected from the group consisting of: R a and R b ;
provided that L does not contain any O—O, N—O, N—N, N—S(O) 0 , or O—S(O) 0-2 bonds;
wherein each R L is independently selected from the group consisting of: halo; cyano; —OH; —C 1-6 alkoxy; —C 1-6 haloalkoxy; —NR d R e ; C(═O)N(R′) 2 ; S(O) 0-2 (C 1-6 alkyl); S(O) 0-2 (C 1-6 haloalkyl); S(O) 1-2 N(R f ) 2 ; —R b ; and C 1-6 alkyl optionally substituted with 1-6 R e ;
VBM is selected from the group consisting of: (V1), (V2), (V3), (V4), (V5), (V6), (V7), (V8), and (V1P):
wherein:
each R 7 and R 8 is independently selected from the group consisting of: H, C 1-6 alkyl, C 1-6 haloalkyl, and C 3-6 cycloalkyl;
R 7a is selected from the group consisting of: halo and CN;
mp is 0, 1, or 2;
each R p is independently selected from the group consisting of: —F, C 1-6 alkyl, C 1-6 haloalkyl, and C 3-6 cycloalkyl;
m9 is 0, 1, 2, or 3;
m10 is 0, 1, or 2; and
each R 9 and R 0 is independently selected from the group consisting of: halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy;
R 11 is C 1-10 alkyl optionally substituted with 1-6 R c ;
each R a is independently selected from the group consisting of:
(a) halo;
(b) cyano;
(c) —OH;
(d) oxo;
(e) —C 1-6 alkoxy;
(f) —C 1-6 haloalkoxy;
(g) —NR d R e ;
(h) C(═O)C 1-6 alkyl;
(i) C(═O)C 1-6 haloalkyl;
(j) C(═O)OH;
(k) C(═O)OC 1-6 alkyl;
(l) C(═O)OC 1-6 haloalkyl;
(m) C(═O)N(R f ) 2 ;
(n) S(O) 0-2 (C 1-6 alkyl);
(o) S(O) 0-2 (C 1-6 haloalkyl);
(p) S(O) 1-2 N(R f ) 2 ; and
(q) C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, each optionally substituted with 1-6 R c ,
each R b is independently selected from the group consisting of: -(L b ) b -R b1 and —R b1 , wherein:
each b is independently 1, 2, or 3;
each -L b is independently selected from the group consisting of: —O—; —N(H)—; —N(C 1-3 alkyl)-; —S(O) 0-2 —; C(═O); and C 1-3 alkylene; and
each R b1 is independently selected from the group consisting of: C 3-10 cycloalkyl, 4-10 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl, each of which is optionally substituted with 1-3 R g ;
each R c is independently selected from the group consisting of: halo; cyano; —OH; —C 1-6 alkoxy; —C 1-6 haloalkoxy; —NR d R e ; C(═O)C 1-6 alkyl; C(═O)C 1-6 haloalkyl; C(═O)OC 1-6 alkyl; C(═O)OC 1-6 haloalkyl; C(═O)OH; C(═O)N(R f ) 2 ; S(O) 0-2 (C 1-6 alkyl); S(O) 0-2 (C 1-6 haloalkyl); and S(O) 1-2 N(R f ) 2 ;
each R d and R e is independently selected from the group consisting of: H; C(═O)C 1-6 alkyl; C(═O)C 1-6 haloalkyl; C(═O)OC 1-6 alkyl; C(═O)OC 1-6 haloalkyl; C(═O)N(R f ) 2 ; S(O) 1-2 (C 1-6 alkyl); S(O) 1-2 (C 1-6 haloalkyl); S(O) 1-2 N(R f ) 2 ; and C 1-6 alkyl optionally substituted with 1-3 R h ,
each R f is independently selected from the group consisting of: H and C 1-6 alkyl optionally substituted with 1-3 R h ;
each R g is independently selected from the group consisting of: R h ; C 1-3 alkyl; and C 1-3 haloalkyl; and
each R h is independently selected from the group consisting of: halo; cyano; —OH; —C 1-6 alkoxy; —C 1-6 haloalkoxy; —NH 2 , —N(H)(C 1-3 alkyl); and —N(C 1-3 alkyl) 2 ;
provided that when VBM is (V1), (V2), or (V3), then L does not contain an adamantylene group.
2 . The compound of claim 1 , wherein Ring A is
wherein aa represents the point of attachment to L; or
Ring A is
wherein aa represents the point of attachment to L; or
Ring A is
wherein aa represents the point of attachment to L.
3 . The compound of claim 1 or 2 , wherein one R a present on Ring A is C 1-3 alkyl optionally substituted with 1-3 F; or
one R a present on Ring A is methyl or CF 3 .
4 . The compound of any one of claims 1-3 , wherein R 1 is C(O)OH.
5 . The compound of any one of claims 1-3 , wherein R 1 is C(O)NHR e .
6 . The compound of any one of claims 1-5 , wherein m2 is 0.
7 . The compound of any one of claims 1-6 , wherein m3 is 0.
8 . The compound of any one of claims 1-7 , wherein m4 is 0.
9 . The compound of any one of claims 1-8 , wherein m5 is 0.
10 . The compound of any one of claims 1-5 , wherein m2 is 0; m3 is 0; m4 is 0; and
m5 is 0.
11 . The compound of any one of claims 1-10 , wherein VBM is (V1):
or
VBM is (V1a):
or
VBM is (V2):
or
VBM is (V2a):
or
VBM is (V3):
or
VBM is (V3a):
or
VBM is (V4):
or
VBM is (V4a):
12 . The compound of claim 11 , wherein one R 7 is H; and the other R 7 is C 1-6 alkyl; or
one R 7 is H; and the other R 7 is tert-butyl.
13 . The compound of any one of claim 11 or 12 , wherein the carbon atom to which each R 7 is attached has (S)-stereogenic configuration.
14 . The compound of any one of claims 11-13 , wherein one R 8 is H; and the other R 8 is C 1-6 alkyl (e.g., methyl).
15 . The compound of any one of claims 11-13 , wherein each R 8 is H.
16 . The compound of any one of claims 11-13 , wherein the carbon atom to which each R 8 is attached has (S)-stereogenic configuration.
17 . The compound of any one of claims 11-16 , wherein m9 is 0.
18 . The compound of any one of claims 11-17 , wherein m10 is 1.
19 . The compound of any one of claims 11-18 , wherein R 0 is C 1-6 alkyl; or R 10 is methyl.
20 . The compound of any one of claims 11-19 , wherein mp is 0.
21 . The compound of any one of claims 1-11 , wherein VBM is:
VBM is:
VBM is:
VBM is:
22 . The compound of any one of claims 1-21 , wherein L is -(L A ) n1 -; and L A and n1 are defined according to (BB).
23 . The compound of claim 22 , wherein n1 is an integer from 3 to 5; or
n1 is an integer from 5 to 9; or n1 is an integer from 9 to 15.
24 . The compound of any one of claim 22 or 23 , wherein 1-4 occurrences of L A is L A3 .
25 . The compound of any one of claims 22-24 , wherein 1-3 occurrences of L A is L A3 .
26 . The compound of any one of claims 22-25 , wherein 1-2 occurrences of L A is L A3 .
27 . The compound of any one of claims 22-26 , wherein 0-2 occurrences of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —.
28 . The compound of any one of claims 22-27 , wherein each occurrence of L A1 is —CH 2 —.
29 . The compound of any one of claims 22-27 , wherein one occurrence of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —.
30 . The compound of any one of claims 1-29 , wherein each R L is independently selected from the group consisting of: —F and —C 1-3 alkyl optionally substituted with 1-3 F.
31 . The compound of any one of claims 1-22 , wherein L is:
-(L A3 ) 0-2 -(L A1 ) 1-15 -(L A3 ) 0-1-bb , wherein bb represents the point of attachment to VBM.
32 . The compound of claim 31 , wherein 0-2 occurrences of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —; or
each occurrence of L A1 is —CH 2 —; or
one occurrence of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —.
33 . The compound of any one of claim 31 or 32 , wherein each R L is independently selected from the group consisting of: —F and —C 1-3 alkyl optionally substituted with 1-3 F.
34 . The compound of claim 31 , wherein L is a divalent group of Formula (L-1):
wherein:
a3a is 0 or 1;
L A3a is selected from the group consisting of: —O—, —N(H)—, and —N(C 1-3 alkyl)-;
a1 is an integer from 1 to 15;
a3b is 0 or 1;
L A3b is independently selected from the group consisting of: C(═O), —O—, N(H)—, and —N(C 1-3 alkyl)-; and
bb represents the point of attachment to VBM.
35 . The compound of claim 36 , wherein a3b is 1.
36 . The compound of claim 36 or 37 , wherein L A3b is C(═O).
37 . The compound of claim 36 or 37 , wherein L A3b is —N(H)—; or
L A3b is —N(C 1-3 alkyl)-.
38 . The compound of claim 36 or 37 , wherein L A3b is —O—.
39 . The compound of claim 36 , wherein a3b is 0.
40 . The compound of any one of claims 36-39 , wherein a3a is 1.
41 . The compound of any one of claims 36-40 , wherein L A3a is 0.
42 . The compound of any one of claims 36-41 , wherein a3a is 0.
43 . The compound of any one of claims 36-42 , wherein a1 is 1 or 2; or
a1 is an integer from 3 to 5; or a1 is an integer from 5 to 9; or a1 is an integer from 9 to 15.
44 . The compound of any one of claims 36-43 , wherein 0-2 occurrences of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —; or
each occurrence of L A1 is —CH 2 —; or
one occurrence of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —.
45 . The compound of claim 44 , wherein each R L is independently selected from the group consisting of: —F and —C 1-3 alkyl optionally substituted with 1-3 F.
46 . The compound of any one of claims 1-21 , wherein L is -(L A ) n1 -; and L A and n1 are defined according to (AA).
47 . The compound of claim 46 , wherein n1 is an integer from 3 to 5; or
n1 is an integer from 5 to 9; or. n1 is 6, 7, or 8; or. n1 is an integer from 9 to 12.
48 . The compound of any one of claim 46 or 47 , wherein 1-2 occurrences of L A is L A4 ; or
wherein one occurrence of L A is L A4 .
49 . The compound of any one of claims 46-48 , wherein each L A4 is independently selected from the group consisting of:
a) C 3-10 cycloalkylene or 4-10 membered heterocyclylene, each of which is optionally substituted with 1-3 R a ; and b) phenylene or 5-6 membered heteroarylene, each of which is optionally substituted with 1-3 R a .
50 . The compound of any one of claims 46-49 , wherein 1-4 occurrences of L A is L A3 ; or
1-2 occurrences of L A is L A3 ; or 2-7 occurrences of L A are L A1 ; or 2-5 occurrences of L A are L A1 .
51 . The compound of any one of claims 46-50 , wherein 0-2 occurrences of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —; or
each occurrence of L A1 is —CH 2 —; or
one occurrence of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —.
52 . The compound of claim 51 , wherein each R L is independently selected from the group consisting of: —F and —C 1-3 alkyl optionally substituted with 1-3 F.
53 . The compound of any one of claims 1-21 or 46 , wherein L is -(L A ) n1 -, and L A and n1 are defined according to (AA), wherein:
n1 is an integer from 5 to 9; 1-2 occurrences of L A is L A4 ; 2-7 occurrences of L A are L A1 ; and 1-3 occurrences of L A is L A3 .
54 . The compound of any one of claims 1-21 or 46 , wherein L is selected from the group consisting of:
(i) -(L A3 ) 0-2 -(L A1 ) 0-5 -L A4 -(L A1 ) 0-5 -L A3 - bb ; (ii) -(L A3 ) 0-2 -(L A1 ) 0-5 -L A4 -(L A1 ) 0-5-bb ; and provided that L contains 2-7 L A1 ; and wherein bb represents the point of attachment to VBM.
55 . The compound of claim 53 or 54 , wherein each L A4 is independently selected from the group consisting of:
a) C 3-10 cycloalkylene or 4-10 membered heterocyclylene, each of which is optionally substituted with 1-3 R a ; and b) phenylene or 5-6 membered heteroarylene, each of which is optionally substituted with 1-3 R a .
56 . The compound of any one of claims 53-55 , wherein 0-1 occurrence of L A1 is —CHR L — or —C(R L ) 2 —; and each remaining occurrence of L A1 is —CH 2 —.
57 . The compound of any one of claims 1 - 36 or 71 , wherein L is:
-(L A3 ) 0-2 -(L A1 ) 0-5 -L A4 _A1) 0-5 -L A3 - bb ;
provided that L contains 2-7 L A1 ; and wherein bb represents the point of attachment to VBM.
58 . The compound of any one of claims 1-21, 46, or 57 , wherein L is:
-(L A3 ) 0-1 -(L A1 ) 0-5 -L A4 _A1) 0-5 -L A3 - bb ; provided that L contains 2-5 L A1 ; and wherein bb represents the point of attachment to VBM.
59 . The compound of claim 57 or 58 , wherein L is a divalent group of Formula (L-2):
wherein:
a3a is 0 or 1;
L A3a and L A3b are independently selected from the group consisting of: —O—, —N(H)—, —N(C 1-3 alkyl)-, and C(═O);
a1a and a1b are independently integers from 0 to 5, provided that a1a+a1b is from 2 to 5;
L A1a and L A1 b are independently selected from the group consisting of: —CH 2 —, —CHR L —, and —C(R L ) 2 —;
L A4 is selected from the group consisting of:
a) C 3-10 cycloalkylene or 4-10 membered heterocyclylene, each of which is optionally substituted with 1-3 R a ; and
b) phenylene or 5-6 membered heteroarylene, each of which is optionally substituted with 1-3 R a ; and
bb represents the point of attachment to VBM.
60 . The compound of claim 59 , wherein a3a is 1.
61 . The compound of claim 59 or 60 , wherein L A3a is —O—.
62 . The compound of claim 59 , wherein a3a is 0.
63 . The compound of any one of claims 59-62 , wherein L A3b is —N(H)— or —N(C 1-3 alkyl)-; or
L A3b is —O—; or
L A3b is C(═O).
64 . The compound of claim 59 , wherein a3a is 1; L A3a is —O—; and L A3b is C(═O).
65 . The compound of claim 59 , wherein a3a is 1; L A3a is —O—; and L A3b is —O—, —N(H)—, or —N(C 1-3 alkyl)-.
66 . The compound of claim 59 , wherein a3a is 0; and L A3b is C(═O).
67 . The compound of claim 59 , wherein a3a is 0; and L A3b is —O—, —N(H)—, or —N(C 1-3 alkyl)-.
68 . The compound of any one of claims 1-21 or 46 , wherein L is:
-(L A3 ) 0-2 -(L A1 ) 0-5 -L A4 _A1) 0-5-bb ; provided that L contains 2-7 L A1 ; and wherein bb represents the point of attachment to VBM.
69 . The compound of any one of claims 1-21, 46, or 68 , wherein L is:
-(L A3 ) 0-1 -(L A1 ) 0-5 -L A4 _A1) 0-5-bb ; provided that L contains 2-5 L A1 ; and wherein bb represents the point of attachment to VBM.
70 . The compound of claim 68 or 69 , wherein L is a divalent group of Formula (L-3):
wherein:
a3a is 0 or 1;
L A3a is selected from the group consisting of: —O—, —N(H)—, and —N(C 1-3 alkyl)-;
a1a and a1b are independently integers from 0 to 5, provided that a1a+a1b is from 2 to 5;
L A1a and L A1b are independently selected from the group consisting of: —CH 2 —, —CHR L —, and —C(R L ) 2 —;
L A4 is selected from the group consisting of:
a) C 3-10 cycloalkylene or 4-10 membered heterocyclylene, each of which is optionally substituted with 1-3 R a ; and
b) phenylene or 5-6 membered heteroarylene, each of which is optionally substituted with 1-3 R a ; and
bb represents the point of attachment to VBM.
71 . The compound of claim 70 , wherein a3a is 1.
72 . The compound of claim 70 or 71 , wherein L A3a is —O—.
73 . The compound of claim 70 , wherein a3a is 0.
74 . The compound of any one of claims 59-67 or 70-73 , wherein a1a+a1b is 2, 3, or 4; or
a1a+a1b is 5.
75 . The compound of any one of claims 59-67, 70-74 , wherein each occurrence of L A1a and L A1b is —CH 2 —; or
L A1a is —CHR L — or —C(R L ) 2 —; each remaining occurrence of L A1a is —CH 2 —; and each occurrence of L A1b is —CH 2 —; or
one occurrence of L A1b is —CHR L — or —C(R L ) 2 —; each remaining occurrence of L A1b is —CH 2 —; and each occurrence of L A1a is —CH 2 —.
76 . The compound of claim 75 , wherein each R L is independently selected from the group consisting of: —F and —C 1-3 alkyl optionally substituted with 1-3 F.
77 . The compound of any one of claims 59-67 or 70-74 , wherein a1b is 2, 3, or 4; one occurrence of L A1b is —CHR L — or —C(R L ) 2 —; each remaining occurrence of L A1b is —CH 2 —; and each occurrence of L A1a is —CH 2 —.
78 . The compound of claim 77 , wherein one occurrence of L A1b is CF 2 , CMe 2 , C(H)F, C(H)Me, or C(H)CF 3 .
79 . The compound of any one of claims 57-78 , wherein L A4 is 4-10 membered heterocyclylene optionally substituted with 1-3 R a .
80 . The compound of any one of claims 57-79 , wherein L A4 is selected from the group consisting of:
each optionally substituted with 1-3 R a at one or more ring carbon atoms, wherein cc represents the point of attachment to L A1b .
81 . The compound of claim 79 or 80 , wherein each R a present on L A4 is independently F or C 1-3 alkyl optionally substituted with 1-3 F.
82 . The compound of any one of claims 57-78 , wherein L A4 is C 3-10 cycloalkylene optionally substituted with 1-3 R a .
83 . The compound of any one of claims 57-78 or 82 , wherein L A4 is 1,4-cyclohexylene optionally substituted with 1-3 R a .
84 . The compound of any one of claims 57-78 , wherein L A4 is phenylene or 5-6 membered heteroarylene, each of which is optionally substituted with 1-3 R a .
85 . The compound of any one of claims 57-78 or 84 , wherein L A4 is phenylene optionally substituted with 1-3 R a ; or
L A4 is 1,2-phenylene optionally substituted with 1-3 R a ; or L A4 is 1,4-phenylene optionally substituted with 1-3 R a .
86 . A compound selected from the group consisting of the compounds in Table C1, or a pharmaceutically acceptable salt thereof.
87 . The compound of claim 86 , wherein the compound does not exhibit Y min (6 h)≥70% and/or Y min (24 h)≥70% under conditions described in Example B1.
88 . A pharmaceutical composition comprising a compound as claimed in any one of claims 1-87 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
89 . A method for treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1-87 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 88 .
90 . The method of claim 89 , wherein the method comprises administering an additional therapy or therapeutic agent.
91 . The method of claim 90 , wherein the additional therapy or therapeutic agent is an ALK inhibitor, a BCL-2 inhibitor, a BCR-Abl inhibitor, a BRaf inhibitor, a CDK2 inhibitor, CDK 4/6 inhibitor, a CDK7 inhibitor, a CDK9 inhibitor, an EGFR inhibitor, an anti-EGFR antibody or an anti-EGFR antibody-drug conjugate, an ERK inhibitor, a FGFR1 inhibitor, a FGFR2 inhibitor, a FGFR3 inhibitor, a FGFR4 inhibitor, a HER2 inhibitor, an anti-HER2 antibody or an anti-HER2 antibody-drug conjugate, a JAK inhibitor, a KRas inhibitor, a MEK inhibitor, a MET inhibitor, a PARP inhibitor, an LSD1 inhibitor, a BET inhibitor, a telomerase inhibitor, a TORC1/2 inhibitor, chemotherapy, radiotherapy, or a combination thereof.
92 . The method of claim 91 , wherein the additional therapy or therapeutic agent is a JAK inhibitor.
93 . The method of claim 92 , wherein the JAK inhibitor is fedratinib (e.g., fedratinib dihydrochloride monohydrate), momelotinib (e.g., momelotinib dihydrochloride), pacritinib (e.g., pacritinib citrate), ruxolitinib (e.g., ruxolitinib phosphate), or a combination thereof.
94 . The method of any one of claims 89-93 , wherein the cancer is breast cancer, colorectal cancer, bile duct cancer, colorectal cancer, gastrointestinal stromal tumor, pancreatic cancer, bladder cancer, kidney cancer, cervical cancer, ovarian cancer, uterine cancer, head and neck cancer, hematological cancer, lung cancer, skin cancer, or a combination thereof.
95 . The method of claim 94 , wherein the hematological cancer is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), small lymphocytic lymphoma (SLL), essential thrombocythemia, polycythemia vera, myelofibrosis, or a combination thereof.
96 . The method of claim 95 , wherein the hematological cancer is essential thrombocythemia, polycythemia vera, myelofibrosis, or a combination thereof.
97 . The method of any one of claims 95-96 , wherein the hematological cancer has a JAK2 mutation (e.g., JAK2 V617F).
98 . Any of the compounds, methods, or uses as provided herein.Cited by (0)
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